DESCRIPTION (Taken from application): Microscopic colitis is an idiopathic, chronic diarrheal syndrome characterized by microscopic mucosal inflammation of an endoscopically normal appearing, non-ulcerated colon. Patients with this disorder suffer considerable physical, emotional, and social disability from frequent passage of liquid stools, sometimes with fecal incontinence. There have been no studies of treatment for this disorder. This application contains a proposal for a placebo-controlled study to assess the efficacy of bismuth subsalicylate therapy in patients with microscopic colitis. The rationale of choosing bismuth subsalicylate for study is that it has known anti-diarrhea, anti-bacterial, and anti-inflammatory properties, and in an uncontrolled pilot study of this treatment for eight weeks in 9 patients with microscopic colitis, 8 achieved complete resolution of diarrhea and 7 resolved their colitis. The first broad, long-term objective of the proposed pilot study is to determine the efficacy and the mechanisms of action of bismuth subsalicylate in microscopic colitis, which in turn may provide clues to its etiology and pathogenesis. The second long-range objective is to develop effective treatment for patients afflicted with microscopic colitis. The research design for this study calls for recruitment of 24 patients with microscopic colitis over a two-year period. Before treatment, they will undergo a 48-hour stool collection, a flexible sigmoidoscopy with random left colon biopsies, and blood work. Patients will then be randomized to treatment with either eight 262 mg tablets of bismuth subsalicylate per day (divided into three doses) or eight placebo tablets per day for eight consecutive weeks. Patients will be evaluated at the mid-study point to monitor for side effects and to confirm compliance. Following eight weeks of treatment, patients will undergo a repeat stool collection and flexible sigmoidoscopy with biopsies to determine the effect of treatment on fecal consistency, fecal frequency, fecal weight, and colonic histologic parameters, including lamina propria inflammation, intraepithelial lymphocytosis, and surface epithelial abnormalities. It is expected that any outcome of this trial will be valuable, as it will begin our understanding of appropriate treatment for patients with microscopic colitis.